Role of SLC transporters in toxicity induced by anticancer drugs. (2nd June 2020)

• Record Type: Journal Article
• Authors: Huang, Kevin M.; Uddin, Muhammad Erfan; DiGiacomo, Duncan; Lustberg, Maryam B.; Hu, Shuiying; Sparreboom, Alex
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 16:Number 6(2020)
• Page Start: 493
• Page End: 506
• Publication Date: 2020-06-02
• Subjects: Organic cation transporters -- solute carriers -- pharmacokinetics -- toxicity -- tyrosine kinase inhibitors -- FDA -- transporter-drug interactions; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2020.1755253
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Introduction: . Membrane transporters are integral to the maintenance of cellular integrity of all tissue and cell types. While transporters play an established role in the systemic pharmacokinetics of therapeutic drugs, tissue specific expression of uptake transporters can serve as an initiating mechanism that governs the accumulation and impact of cytotoxic drugs. Areas covered: . This review provides an overview of organic cation transporters as determinants of chemotherapy-induced toxicities. We also provide insights into the recently updated FDA guidelines for in vitro drug interaction studies, with a particular focus on the class of tyrosine kinase inhibitors as perpetrators of transporter-mediated drug interactions. Expert opinion: . Studies performed over the last few decades have highlighted the important role of basolateral uptake and apical efflux transporters in the pathophysiology of drug-induced organ damage. Increased understanding of the mechanisms that govern the accumulation of cytotoxic drugs has provided insights into the development of novel strategies to prevent debilitating toxicities. Furthermore, we argue that current regulatory guidelines provide inadequate recommendations for in vitro studies to identify substrates or inhibitors of drug transporters. Therefore, the translational and predictive power of FDA-approved drugs as modulators of transport function remains ambiguous and warrants further revision of the current guidelines.